title: Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-α and IL-6 receptor targeted therapies in refractory Takayasu arteritis.
abstract: OBJECTIVE
  We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease.
  
  
  METHODS
  Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated.
  
  
  RESULTS
  Nine patients were treated with biologic therapies. All had previously received high dose prednisolone and ≥1 conventional immunosuppressant. Five patients had failed cyclophosphamide. The patients prescribed biologics had more extensive arterial injury than the remainder of the cohort and persistent active disease (ITAS range 2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNF-α therapy, three IL-6R blockade. The mean duration of anti-TNF-α treatment was 42 months (maximum 8 years). One patient developed new arterial stenoses while receiving anti-TNF-α and subsequently achieved disease remission with tocilizumab. Two patients have now demonstrated sustained responses to IL-6R inhibition at 19 and 20 months. Following introduction of biologic therapy, serial non-invasive imaging has revealed no significant progression in arterial injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS (p<0.01) was observed, with no increase in TADs.
  
  
  CONCLUSIONS
  We report for the first time sustained responses to both anti-TNF-α and IL6R antagonists in refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non-responders, we propose that biologics should now be considered ahead of cyclophosphamide in these young patients.
authors.affiliation: Rheumatology Section, Imperial College London, Hammersmith Hospital, London, UK. taryn.youngstein@chelwest.nhs.uk.
authors.forename: Taryn
authors.initials: T
authors.lastname: Youngstein
authors.forename: James E
authors.initials: JE
authors.lastname: Peters
authors.forename: Shahir S
authors.initials: SS
authors.lastname: Hamdulay
authors.forename: Devesh
authors.initials: D
authors.lastname: Mewar
authors.forename: Alec
authors.initials: A
authors.lastname: Price-Forbes
authors.forename: Mark
authors.initials: M
authors.lastname: Lloyd
authors.forename: Rachel
authors.initials: R
authors.lastname: Jeffery
authors.forename: Anne R
authors.initials: AR
authors.lastname: Kinderlerer
authors.forename: Justin C
authors.initials: JC
authors.lastname: Mason
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D001691:Biological Therapy / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D016903:Drug Monitoring; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013625:Takayasu Arteritis / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003520:Cyclophosphamide; C502936:tocilizumab; D011241:Prednisone